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Abstract
Background: During the past decade, a number of new hormonal therapies (HTs) have been developed,
including the selective estrogen receptor modulators (SERMs), aromatase inhibitors
(AIs), and estrogen receptor (ER) antagonists. Their uses in breast cancer are continually
evolving as new clinical trial results become available. Although tamoxifen, the most
widely used HT for breast cancer, was originally approved for and used in the treatment
of metastatic breast cancer (MBC), its effectiveness as MBC therapy led to its subsequent
assessment and use as adjuvant and risk-reduction therapy for breast cancer. However,
tamoxifen is not universally effective in these settings and is associated with infrequent
known toxicities such as increased risk of thromboembolism and endometrial cancer;
therefore, a search for more effective and more tolerable HTs has evolved.
Objective: This article reviews the data supporting the use of newer HTs as initial treatment
of MBC and their potential use as adjuvant, neoadjuvant, and chemopreventive therapies.
Methods: Articles for inclusion in this manuscript were identified through the following searches,
limited to English-language publications: MEDLINE (mid 1960s to January 2002), American
Society of Oncology abstracts (1997–2001), and San Antonio Breast Cancer Symposium
abstracts (2001 and 2002). The following search terms were used: breast cancer, breast cancer guidelines, hormonal therapies, tamoxifen, toremifine,
letrozole, anastrozole, exemestane, megestrol acetate, fulvestrant, and ICI 182,780.
Results: Recent studies have focused on newer agents as initial and subsequent treatment of
MBC, adjuvant or neoadjuvant treatments of breast cancer, and chemopreventive agents
in both healthy women and women with a history of ductal carcinoma in situ (DCIS).
Results of clinical trials comparing AIs with tamoxifen as first-line MBC treatment
show that AIs are as effective as, or more effective than, tamoxifen and are associated
with fewer serious adverse events. Tamoxifen remains the gold standard for adjuvant
therapy. However, preliminary results of ongoing clinical trials comparing tamoxifen
with anastrozole suggest that anastrozole may be the superior agent. Both tamoxifen
and the AIs have been shown to be active in the neoadjuvant treatment of breast cancer.
Trial results have shown that tamoxifen is effective for breast cancer prevention
in patients at high risk of developing breast cancer but who are otherwise healthy,
patients with a history of DCIS, and patients with lobular carcinoma in situ.
Conclusions: Although tamoxifen has been the gold standard of HT for breast cancer, results of
ongoing trials assessing the newer HTs as initial, neoadjuvant, adjuvant, and chemopreventive
therapies may substantially change our current clinical practice patterns.
Keywords
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References
- Tamoxifen in the treatment of breast cancer.N Engl J Med. 1998; 339: 1609-1618
- Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma.Cancer. 2001; 92: 2247-2258
- Superior efficacy of letrozole versus tamoxifen as first-line therapy for post-menopausal women with advanced breast cancer: Results of a phase III stu.J Clin Oncol. 2001; 19: 2596-2606
- Exemestane as neoadjuvant treatment for locally advanced breast cancer: Endocrinologic and clinical endpoints.Breast Cancer Res Treat. 2000; 64 (Abstract 170): 53
- The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in post-menopausal women with breast cancer: A randomized, double-blind, single-cente.Clin Cancer Res. 2000; 6: 2229-2235
- National Institutes of Health Consensus Development Conference Statement: Adjuvant therapy for breast cancer, November 1–3, 2000.J Natl Cancer Inst. 2001; 93: 979-989
NCCN Practice Guidelines in Oncology, Breast Cancer, version 2.2002. Available at: http://www.nccn.org. Accessed February 1, 2002.
- Tamoxifen for early breast cancer: An overview of the randomised trials.Lancet. 1998; 351: 1451-1467
- Adjuvant therapy of primary breast cancer: A review of key findings from the 7th International Conference.Oncologist. 2001; 6: 376-385
- Phase II study of tamoxifen: Report of 74 patients with stage IV breast cancer.Cancer Treat Rep. 1976; 60: 1431-1435
- First IBIS results show tamoxifen reduces breast cancer in healthy high-risk women—but still too early to know if benefits outweight risks.Presented at: 3rd European Breast Cancer Conference. March 20, 2002 (Barcelona, Spain)
- Endocrine therapy in metastatic breast cancer.Cancer Treat Res. 1998; 94: 231-254
- Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer.J Clin Oncol. 1995; 13: 2556-2566
- Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: A randomized double-blind, the ‘Nordic’ phase III s.Br J Cancer. 1997; 76: 270-277
- Final survival analysis of the double-blind, randomized, multinational phase III trial of letrozole (Femara®) compared to tamoxifen as first-line hor.Paper presented at: 24th Annual San Antonio Breast Cancer Symposium. December 10–13, 2001 (San Antonio, Tex.)
- A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer.Breast Cancer Res Treat. 1997; 45: 251-262
- Phase III randomized trial of toremifene vs tamoxifen in hormonodependent advanced breast cancer.Breast Cancer Res Treat. 2001; 65: 119-124
- Exemestane (Aromasin) is active and well tolerated as first-line hormonal therapy (HT) of metastatic breast cancer (MBC) patients (Pts): Results of a r.Program and Abstracts of the 36th Annual Meeting of the American Society of Clinical Oncology. May 20–23, 2000 (New Orleans, La. Abstract 316)
- Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer.J Clin Oncol. 1999; 17: 3418-3425
- Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: A phase II trial.J Clin Oncol. 2000; 18: 2234-2244
- Fulvestrant.Drugs. 2001; 61: 807-813
- Estrogen receptor downregulators: New antihormonal therapy for advanced breast cancer.Clin Ther. 2002; 24: 17-30
- Combination endocrine therapy in the management of breast cancer.Oncologist. 2001; 6: 538-546
- The effect of alternating letrozole and tamoxifen in comparison to sequential treatment with each drug alone or in combination.Breast Cancer Res Treat. 2001; 69 (Abstract 444): 287
- Role of adjuvant endocrine therapy in early-stage breast cancer.Semin Oncol. 2001; 28: 313-321
- Adjuvant trials of toremifene vs tamoxifen: The European experience.Oncology. 1998; 12: 23-27
- Aromatase inhibition and anti-estrogen therapy in early breast cancer treatment and chemoprevention.Oncology. 2001; 15: 28-34
- Aromatase inhibitors in the treatment and prevention of breast cancer.J Clin Oncol. 2001; 19: 881-894
- The ATAC (Arimidex, Tamoxifen, Alone or in Combination) adjuvant breast cancer trial in postmenopausal (PM) women.Paper presented at: 24th Annual San Antonio Breast Cancer Symposium. December 10–13, 2001 (San Antonio, Tex.)
- Sequential tamoxifen and amino-glutethimide versus tamoxifen alone in the adjuvant treatment of postmenopausal breast cancer patients: Results of an It.J Clin Oncol. 2001; 19: 4209-4215
- Hormonal treatment for metastatic breast cancer.Cancer. 1994; 73: 354-361
- The effect of anastrozole (Arimidex™) on serum lipids—data from a randomized comparison of anastrozole (AN) versus tamoxifen (TAM) in post-menopaus.Breast Cancer Res Treat. 2000; 64 (Abstract 164): 51
- Preoperative treatment of post-menopausal breast cancer patients with letrozole: A randomized double-blind multicenter study.Ann Oncol. 2001; 12: 1527-1532
- Neoadjuvant tamoxifen for operable breast cancer: A need for phase III studies?.Cancer Detect Prev. 2000; 24: 445-451
- Estrogen and the risk of breast cancer.N Engl J Med. 2001; 344: 276-285
- Treatment of breast cancer.N Engl J Med. 1998; 339: 974-984
- Tamoxifen for the prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study.J Natl Cancer Inst. 1998; 90: 1371-1388
- Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial.Lancet. 1998; 352: 98-101
- Prevention of breast cancer with tamoxifen: Preliminary findings from the Italian randomised trial among hysterectomised women.Lancet. 1998; 352: 93-97
- The effect of raloxifene on risk of breast cancer in postmenopausal women. Results from the MORE randomized trial.JAMA. 1999; 281: 2189-2197
- Selective estrogen receptor modulators: Structure, function, and clinical use.J Clin Oncol. 2000; 18: 3172-3186
- The study of tamoxifen and raloxifene: Preliminary enrollment data from a randomized breast cancer risk reduction trial.Breast Cancer Res Treat. 2001; 69 (Abstract 135): 225
- Use of letrozole as a chemopreventive agent in the aromatase overexpression transgenic mouse model.Breast Cancer Res Treat. 2001; 69 (Abstract 449): 289
- Combined estrogen blockade of the breast with raloxifene and exemestane in postmenopausal women for breast cancer prevention.Breast Cancer Res Treat. 2001; 69 (Abstract 138): 226
- Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial.Lancet. 1999; 353: 1993-2000
Article info
Publication history
Accepted:
April 2,
2002
Identification
Copyright
© 2002 Published by Elsevier Inc.
